1. Field
Disclosed herein are methods for modification of chitosan that increases their versatility as sorbents, particularly as sorbents of radioisotopes, as well the ability of these materials to function in environments where radioactivity is present. Also disclosed are the materials themselves, as well as methods of using them to separate and purify radioisotopes, and to separate and purify contaminated materials, in particular those radioactive and nonradioactive streams contaminated by metal ions, particularly those of heavy metals.
2. Description of Related Art
Radioactive isotopes are widely used, particularly in the field of nuclear medicine, both for therapy and imaging. However, these materials can present production, storage, and disposal challenges due to their radioactivity, as well as their often significant half-lives.
More particularly, in the radiopharmaceutical area, 99mTc (having a half-life t1/2=6 h), is one of the most widely used radioisotopes in diagnostic medicine, obtained from the decay product of parent 99Mo (t1/2=66 h). 99mTc is a pure gamma emitter (0.143 MeV) ideal for use in medical applications due to its short half-life (6 hours). It is used in 80-85% of the approximately 25 million diagnostic nuclear medicine procedures performed each year.
The parent 99Mo can be produced by the irradiation of 98Mo with thermal/epithermal neutrons in a nuclear reactor, but much of the world supply of 99Mo comes from the fission product of highly enriched uranium (HEU) in a reactor. The HEU process generates large quantities of radioactive waste and does not permit reprocessing of the unused uranium targets due to weapons proliferation concerns.
Low enriched uranium (LEU, 20 percent 235U or less) could be used as a substitute, but would yield large volumes of waste due to the large quantities of un-useable 238U present. Currently, most of the world supply of 99Mo comes from sources outside of the United States. Recent 99Mo production outages at these sources have disrupted medical procedures and have demonstrated the unreliability of this supply chain. This stresses the need for economically feasible alternative sources to produce 99mTc from 99Mo.
The main concerns with neutron capture-produced 99Mo, as compared to the more common fission-produced material described above, involves both lower curie yield and lower specific activity. The specific activity is significantly lower and is of great concern due to impacts on 99Mo/99mTc generator size, efficiency, and functionality. Therefore, use of lower specific activity molybdate is only feasible with a more efficient sorbent to reduce the generator size and to yield a usable dose at the radiopharmacy. Several research works have been focused on the uses of a molybdenum gel generator. See Marageh, M. G., et al., “Industrial-scale production of 99mTc generators for clinical use based on zirconium molybdate gel,” Nuclear Technology, 269, 279-284 (2010); Monoroy-Guzman, F. et al., “99Mo/99mTc generators performances prepared from zirconium molybdate gels” J. Braz. Chem. Soc., 19, 3, 380-388 (2008). Others focused on preparation of 99Mo/99mTc generator based on polymeric or inorganic oxide as an adsorbent material for 99Mo. See Masakazu, T. et al., “A 99mTc generator using a new organic polymer absorbent for (n,γ) 99Mo,” Appl. Radia. Isot., 48, 5, 607-711 (1997); Qazi, Q. M. et al., “Preparation and evaluation of hydrous titanium oxide as a high affinity adsorbent for molybdenum (99Mo) and its potential for use in 99mTc generator,” Radiochim. Acta, 99, 231-235 (2011).
However, such medical uses require that the 99mTc be produced in highly purified form. For example, when 99mTc is produced from the decay of 99Mo, it is important to achieve a high degree of separation of the two elements in order to meet regulatory requirements.
One approach to achieving this level of purity is to separate 99mTc from 99Mo using a highly efficient, selective sorbent, e.g., by sorbing 99Mo and eluting 99mTc. Attempts have been made to use alumina as such a sorbent. However, this alumina provides an efficiency for Mo99 of about 25 mg/g of sorbent. Accordingly, there remains a need in the art for a sorbent that is both efficient in the adsorption of 99Mo, and resistant to the adverse effects of ionizing radiation. In addition, there remains a need for a sorbent that is highly selective for 99Mo, i.e., that is capable of sorbing 99Mo while providing good release of 99mTc.
More generally, there remains a need for a sorbent that is readily available, or producible from readily available materials, and that is customizable by modification to have one or more functional groups (which may be the same or different) allowing the material to remove constituents from a process stream requiring such purification, and that is resistant to degradation by ionizing radiation.
The ion exchange process, which has been used for decades to separate metal ions from aqueous solution, is often compared to adsorption. The primary difference between these two processes is that ion exchange is a stoichiometric process involving electrostatic forces within a solid matrix, whereas in adsorptive separation, uptake of the solute onto the solid surface involves both electrostatic and Van der Waals forces. In an attempt to find a suitable ion exchange resin for the removal of cesium and strontium from waste solution, several investigators have tried a number of inorganic, organic, and bio-adsorbents, with a varying degree of success. See Gu, D., Nguyen, L., Philip, C. V., Huckmen, M. E., and Anthony, R. G. “Cs+ ion exchange kinetics in complex electrolyte solutions using hydrous crystalline silicotitanates”, Ind. Eng. Chem. Res., 36, 5377-5383, 1997; Pawaskar, C. S., Mohapatra, P. K., and Manchanda, V. K. “Extraction of actinides fission products from salt solutions using polyethylene glycols (PEGs)” Journal of Radioanalytical and Nuclear Chemistry, 242 (3), 627-634, 1999; Dozol, J. F., Simon, N., Lamare, V., et al. “A solution for cesium removal from high salinity acidic or alkaline liquid waste: The Crown calyx[4]arenas” Sep. Sci. Technol., 34 (6&7), 877-909, 1999; Arena, G., Contino, A., Margi, A. et al. “Strategies based on calixcrowns for the detection and removal of cesium ions from alkali-containing solutions. Ind. Eng. Chem. Res., 39, 3605-3610, 2000.
However, major disadvantages with the ion exchange process are the cost of the material and regeneration for repeated use when treating radioactive streams. See Hassan, N., Adu-Wusu, K., and Marra, J. C. “Resorcinol-formaldehyde adsorption of cesium (Cs+) from Hanford waste solutions-Part I: Batch equilibrium study” WSRC-MS-2004. The cost of disposal is also a major issue. The success of adsorption processes depends largely on the cost and capacity of the adsorbents and the ease of regeneration.
Chitosan is a partially acetylated glucosamine polymer encountered in the cell walls of fungi. It results from the deacetylation of chitin, which is a major component of crustacean shells and available in abundance in nature. This biopolymer is very effective in adsorbing metal ions because of its ability for complexation due to high content of amino and hydroxyl functional groups. In their natural form, chitosan is soft and has a tendency to agglomerate or form gels in acidic medium. Moreover, chitosan, in its natural form, is non-porous and the specific binding sites of this biopolymer are not readily available for sorption. However, it is necessary to provide physical support and chemical modification to increase the accessibility of the metal binding sites for process applications. It is also essential that the metal binding functional group should be retained after any such modification.
It is well known that polysaccharides can be degraded due to scission of glycoside bonds by ionizing radiation. IAEA-TECDOC-1422, “Radiation processing of polysaccharides' International Atomic Energy Agency, November, 2004. The hydrogel based on polysaccharides and their derivatives has been extensively studied, but very limited work has been reported so far on the impact of radiation on the chitosan-based microporous composite materials and their metal ion uptake capacity.
Chitosan is a non-toxic, biodegradable material. It has been investigated for many new applications because of its availability, polycationic character, membrane effect, etc. The amino group present in the chitosan structure is the active metal binding site, but it also renders chitosan soluble in weak acid. In acidic media, chitosan tends to form a gel which is not suitable for adsorption of metal ions in a continuous process.
Several reports indicated that the cross-linking of chitosan with gluteraldehyde make chitosan acid or alkali resistant. See Elwakeel, K. Z., Atia, A. A., and Donia, A. M. “Removal of Mo(VI) as oxoanions from aqueous solutions using chemically modified magnetic chitosan resins, Hydrometallurgy, 97, 21-28, 2009; Chassary, P., Vincent, T., and Guibal, E. “Metal anion sorption on chitosan and derivative materials: a strategy for polymer modification and optimum use” Reactive and Functional Polymers, 60, 137-149, 2004; Velmurugan, N., Kumar, G. G., Han, S. S., Nahm, K. S., and Lee, Y. S. “Synthesis and characterization of potential fungicidal silver nano-sized particles and chitosan membrane containing silver particles” Iranian Polymer Journal, 18 (5), 383-392, 2009. Gluteraldehyde is a five carbon molecule terminated at both ends by aldehyde groups which are soluble in water and alcohol, as well as in organic solvents. It reacts rapidly with amine groups of chitosan during cross-linking through Schiff's reaction and generates thermally and chemically stable cross-links. See Migneault, I., Dartiguenave, C., Bertrand, M. J., and Waldron, K. C. “Gluteraldehyde: behavior in aqueous solution, reaction with proteins, and application to enzyme crosslinking” Bio Techniques, 37 (5), 790-802, 2004. The amine groups are also considered as the active metal binding sites of chitosan. Therefore, by cross-linking with gluteraldehyde, the chitosan is reported to be acid or alkali resistant but the metal adsorption capacity will be reduced.
Li and Bai (2005) proposed a method to cap the amine group of chitosan by formaldehyde treatment before cross-linking with gluteraldehyde, which was then removed from the chitosan structure by washing thoroughly with 0.5M HCl solution. Li, Nan, and Bai, R. “A novel amine-shielded surface cross-linking of chitosan hydrogel beads for enhanced metal adsorption performance” Ind. Eng. Chem. Res., 44, 6692-6700, 2005.
Crosslinking of chitosan with different functional groups is thought to depend mainly on the crosslinking reaction conditions, such as pH, temperature, ionic concentration, and the surface charge of the materials.
Sing et al. (2006) showed that swelling properties of chitosan hydrogel cross-linked with formaldehyde depends on the responsive behavior of pH, temperature, and ionic strength. Singh, A., Narvi, S. S., Dutta, P. K., and Pandey, N. D. “External stimuli response on a novel chitosan hydrogel crosslinked with formaldehyde” Bull. Mater. Sci., 29 (3), 233-238, 2006.
The surface charge of the chitosan that determines the type of bond that will form between the cross-linking agent and chitosan, depends on the pH of the solution. Hasan, S., Krishnaiah, A., Ghosh, T. K., Viswanath, D. S., Boddu, V. M., and Smith, E. D. “Adsorption of divalent cadmium from aqueous solutions onto chitosan-coated perlite beads, Ind. Eng. Chem. Res., 45, 5066-5077, 2006. The point of zero charge (PZC) value of pure chitosan is in the pH range of 6.2-6.8. See Hasan, S., Ghosh, Viswanath, D. S., Loyalka, S. K., and Sengupta, B. “Preparation and evaluation of fullers earth for removal of cesium from waste streams” Separation Science and Technology, 42 (4), 717-738, 2007. Chitosan is not soluble in alkaline pH, but at acidic pH, the amine groups present in the chitosan can undergo protonation to NH3+ or (NH2—H3O)+.
Li et al. (2007) reported cross-linked chitosan/polyvinyl alcohol (PVA) beads with high mechanical strength. They observed that the H+ ions in the solution can act as both protection of amino groups of chitosan during the crosslinking reaction. Li, M., Cheng, S., and Yan, H. “Preparation of crosslinked chitosan/poly(vinyl alcohol) blend beads with high mechanical strength”, Green Chemistry, 9, 894-898, 2007.
Farris et al. (2010) studied the reaction mechanism for the cross-linking of gelatin with gluteraldehyde. Farris, S., Song, J., and Huang, Q. “Alternative reaction mechanism for the cross-linking of gelatin with gluteraldehyde” J. Agric. Food Chem., 58, 998-1003, 2010. They suggested that, at higher pH values, the cross-linking reaction is governed by Schiff's base reaction, whereas at low pH, the reaction may also involve —OH groups of hydroxyproline and hydroxylysine, leading to the formation of hemiacetals.
Hardy et al. (1969) proposed that, at acidic pH, gluteraldehyde is in equilibrium with its cyclic hemiacetal and polymers of the cyclic hemiacetal and an increase in temperature produces free aldehyde in acid solution. Hardy, P. M., Nicholas, A. C., and Rydon, H. N. “The nature of gluteraldehyde in aqueous solution” Journal of the Chemical Society (D), 565-566, 1969.
Several studies focused on chitosan-based cross-linked material for medical and radiopharmaceutical uses with some success. See, e.g., Hoffman, B., Seitz, D., Mencke, A., Kokott, A., and Ziegler, G. “Gluteraldehyde and oxidized dextran as crosslinker reagents for chitosan-based scaffolds for cartilage tissue engineering” J. Mater Sci: Mater Med, 20(7), 1495-1503, 2009; Salmawi, K. M. “Gamma radiation-induced crosslinked PVA/Chitosan blends for wound dressing” Journal of Macromolecular Science, Part A: Pure and Applied Chemistry, 44, 541-545, 2007; Desai, K. G., and Park, H. J. “Study of gamma-irradiation effects on chitosan microparticles” Drug Delivery, 13, 39-50, 2006; Silva, R. M., Silva, G. A., Coutinho, O. P., Mano, J. F., and Reis, R. L. “Preparation and characterization in simulated body conditions of gluteraldehyde crosslinked chitosan membranes” Journal of Material Science: Materials in Medicine, 15 (10), 1105-1112, 2004.
However, Sabharwal et al. (2004) reported that the radiation processing of natural polymers has drawn less attention as the natural polymers undergo chain scission reaction when exposed to high energy radiation. Sabharwal, S., Varshney, L., Chaudhary, A. D., and Ramnani, S. P. “Radiation processing of natural polymers: Achievements & Trends” In Radiation processing of polysaccharides, 29-37, IAEA, November, 2004. It is reported that irradiation of chitosan yields lower viscosity and chain scission of chitosan. See Kume, T., and Takehisa, M. “Effect of gamma-irradiation on sodium alginate and carrageenan powder” Agric. Biol. Chem. 47, 889-890, 1982; Ulanski, P., and Rosiak, J. M. “Preliminary studies on radiation induced changes in chitosan” Radiat. Phys. Chem. 39(1), 53-57, 1992. The H+ and OH− radicals formed by radiolysis during irradiation of water accelerate the molecular chain scission of chitosan. The reaction between the above free radical and chitosan molecules leads to rapid degradation of chitosan in aqueous solution. See IAEA-TECDOC-1422, “Radiation processing of polysaccharides' International Atomic Energy Agency, November, 2004. These studies suggest that the use of chitosan in environments where it will be exposed to irradiation and potential radiolysis is problematic.
Nevertheless, the current demands for biocompatible polymeric materials in radiopharmaceutical and radioactive waste treatment have increased the interest in developing economically feasible alternative sources of acidic, alkaline, and radiation resistant polymer network structures. Recent development of chitosan-based materials in the area of medical, radiopharmaceuticals, and radioactive waste has drawn attention due to their availability and biocompatibility. See Alves, N. M., and Mano, J. F. “Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications” International Journal of Biological Macromolecules, 43, 401-414, 2008; Berger, J., Reist, M., Mayer, J. M., Felt, O., Peppas, N. A., and Gurny, R. “Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications, European Journal of Pharmaceutics and Biopharmaceutics, 57, 19-34, 2004. It is reported that the chemical changes in chitosan occur due to irradiation and the extent of radiation-induced reaction depends on the polymer network structure. See Zainol, I., Akil, H. M., and Mastor, A. “Effect of γ-ray irradiation on the physical and mechanical properties of chitosan powder” Material Science and Engineering C, 29, 292-297, 2009; Chang, K. P., Cheng, C. H., Chiang, Y. C., Lee, S. C. et al., “Irradiation of synthesized magnetic nanoparticles and its application for hyperthermia” Advanced Materials Research, 47-50, 1298-1301, 2008; Casmiro, M. H., Botelho, M. L., Leal, J. P., and Gil, M. H. “Study on chemical, UV and gamma radiation-induced grafting of 2-hydroxyethyl methacrylate onto chitosan” Radiation Physics and Chemistry, 72, 731-735, 2005; Park et al. “Radioactive chitosan complex for radiation therapy” U.S. Pat. No. 5,762,903, Jun. 9, 1998; Wenwei, Z., Xiaoguang, Z., Li, Yu, Yuefang, Z., and Jiazhen, S. “Some chemical changes in chitosan induced by γ-ray irradiation” Polymer Degradation and Stability, 41, 83-84, 1993; Lim, L. Y., Khor, E., and Koo, O. “γ irradiation of chitosan” Journal of Biomedical Material Research, 43 (3), 282-290, 1998; Yoksan, R., Akashi, M., Miyata, M., and Chirachanchai, S. “Optimal γ-ray dose and irradiation conditions for producing low molecular weight chitosan that retains its chemical structure” Radiation Research, 161, 471-480, 2004; Lu, Y. H., Wei, G. S., and Peng, J. “Radiation degradation of chitosan in the presence of H2O2” Chinese Journal of Polymer Science, 22 (5), 439-444, 2004. However, there is very limited information available on the radiation effect on cross-linked chitosan composite matrices.